The disclosure relates generally to the field of coatings for articles intended for permanent or temporary implantation into animals such as humans.
Infection is a serious complication of devices implanted in the human body (Klevens et al., 2007, J. Am. Med. Assoc. 298:1763). Deep infections, which are difficult to treat may often require removal of the infected implant to eradicate infection and this remains a serious complication of major orthopedic medical procedures utilizing endoprostheses (Rabih et al., 2004, N. Eng. J. Med. 350:1422; Fitzgerald, 1995, J. Am. Acad. Ortho. Surg. 3:249; Khan et al., 2008, J. Ayub. Med. Coll. Abbottabad 20:23). Treatment of deep infections is challenging because it is difficult to supply antibiotics to the infection site, and such treatment can vary from 3 to 14 months in duration (Darouiche, 2004, N. Eng. J. Med. 350:1422) and can include secondary surgery (Furno et al., 2004, J. Antimicrob. Chemother. 54:1019).
The most well-known medical procedures involving orthopedic implants are knee and hip replacement surgeries, with an estimated 940,000 such procedures performed in the U.S. in 2005 (Merrill et al., 2007, Statistical Brief 34, Healthcare Cost and Utilization Project). Other known joint replacement procedures include those of the shoulder, elbow, finger, and ankle.
Titanium implants are used to stabilize fused vertebrae (Foley et al., 2002, Clin. Neurosurg. 49:499; Foley et al., 2003, Spine 28:S26). Another orthopedic use of titanium in the body is to provide alignment for a healing bone with either internal or partially external fixation devices (Rantanen et al., 1998, J. Orthop. Trauma 12:249). Although infection is high in hip (˜0.75%) and knee (1.5%) replacements, it is even higher in trauma cases (greater than 10%) with open wounds (Ridgeway et al., 2005, J. Bone Joint Surg. Br. 87:844; Wilson et al., 2008, Infect. Control Hosp. Epidemiol. 29:219; Agency for Healthcare Research and Quality, 2003, “Total Knee Replacement Summary—Evidence Report/Technology Assessment”, US Department of Health and Human Services; Miclau et al., 2010, J. Orthop. Trauma. 24:583).
Infection rates have increased substantially in recent years. Between the years of 1999 and 2005, infection contracted during hospital visits increased by 62% while the number of hospital visits increased by only 8% (Klein et al., 2007, Emerg. Inf. Dis. 13:1840). Although antibiotics and procedures improved over this time period, infection rates nonetheless increased at an accelerated rate. This can be explained by rapidly increasing development of drug-resistant bacterial strains (Miclau et al., 2010, J. Orthop. Trauma. 24:583).
Development of antibiotic resistance has been recognized as a significant threat to public health and, as a result, is among the highest priorities of several expert committees such as the Institute of Medicine, the American Society for Microbiology, and the U.S. Office of Technology Assessment (Forum on Emerging Infections, 1998, “Antimicrobial Resistance: Issues and Options,” Institute of Medicine, Washington D.C.; American Society of Microbiology, 1997, “New and Reemerging Infectious Diseases: A Global Crisis and Immediate Threat to the Nation's Health, The Role of Research,” Washington D.C.; Office of Technology Assessment, 1994, “Impacts of Antibiotic Resistant Bacteria,” Report OTA-H-629, U.S. Congress, Washington, D.C.; Report of the ASM Task Force on Antibiotic Resistance, 1994, American Society of Microbiology, Washington D.C.). Clearly, antibiotic use must be limited and alternative treatments must be sought.
Due to the large number of patients and the significant percentage of that group who develop infection, almost any contribution in this area can be important for improving both patient recovery and the financial cost of implantation procedures. When a patient gets an infection, the stay in the hospital is extended by six days on average. This represents a significant increase in cost of treatment impacting health care related costs for everyone. The monetary impact of infection alone is exceeding $40 billion annually (Douglas et al., 2009, “The Direct Medical Costs of Healthcare-Associated Infections in U.S. Hospitals and the Benefits of Prevention”, Report of the U.S. Centers for Disease Control and Prevention).
Others have previously recognized the antimicrobial properties of silver (Ag), especially in a micro- or nanoparticulate form, and there is extensive literature reporting that effect. Those observations have motivated others to attempt to incorporate Ag into and onto implantable medical devices. Others have described bactericidal coatings containing Ag nanoparticles in polymers, for example. Ag nanoparticles exhibit higher solubility of Ag and Ag ions than continuous Ag films due to their large surface to volume ratio. However, such polymer carriers can be detrimental to the patient.
A common shortcoming of known Ag-containing coatings is that efforts to improve adherence of such coatings (e.g., to provide durability and scratch-resistance) can adversely affect their antimicrobial properties. Conversely, efforts to improve the antimicrobial efficacy of Ag-containing coatings can adversely affect their ability to stably adhere to implant surfaces.
The subject matter disclosed herein overcomes at least some of these shortcomings by providing Ag-containing coatings (and methods of making them) that exhibit both favorable antimicrobial properties and favorable (i.e., stable and durable) physical properties.